Sodium Bicarbonate → (3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

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Reaction Steps

Intermediate 55A (0.165 g, 0.43 mmol), intermediate 84A (3-methylpyrrolidin-3-yl)methanol hydrochloride (0.099 g, 0.65 mmol) and TEA (0.241 mL, 1.74 mmol) were mixed in dichloromethane (4 mL). The mixture was stirred at RT for 30 min and then sodium triacetoxyhydroborate (0.184 g, 0.87 mmol) was added and the mixture was stirred at RT overnight. Aqueous NaHCO3 (sat., 4 mL) and dichloromethane (4 mL) were added and the mixture was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by preparative reverse-phase HPLC at pH 10 than re-purified at pH3 to give 21 mg (10%). 1H NMR (600 MHz, DMSO) δ 1.01 (s, 3H), 1.31-1.39 (m, 1H), 1.57-1.65 (m, 1H), 2.07 (d, 1H), 2.43-2.49 (m, 2H), 3.13-3.25 (m, 3H), 3.46-3.53 (m, 2H), 3.88 (s, 3H), 4.06-4.14 (m, 1H), 4.51-4.67 (m, 2H), 5.05-5.19 (m, 2H), 6.85 (d, 2H), 7.15-7.31 (m, 4H), 8.02 (d, 2H), LC purity: 93%.

Provenance & Evidence